2',3',5'-Triacetyluridine is a prodrug of uridine .1 It is more lipid soluble than uridine and resistant to degradation by uridine phosphorylase. It is cleaved by plasma esterases in vivo to release uridine. 2',3',5'-Triacetyluridine (6% in the diet) decreases neurodegeneration in the piriform cortex and striatum, as well as reduces the amount of huntingtin-positive aggregates and increases BDNF protein levels in the piriform cortex in a transgenic mouse model of Huntington's disease.2 It also improves rotarod performance and increases survival in transgenic mouse models of Huntington's disease. 2',3',5'-Triacetyluridine reverses toxicity and increases survival in a mouse model of dihydropyrimidine dehydrogenase (DPD) deficiency-induced 5-fluorouracil overdose when used at a concentration of 2,000 mg/kg three times per day beginning within 24 hours of 5-FU administration.3 Formulations containing 2',3',5'-triacetyluridine have been used in the treatment of hereditary orotic aciduria and of overdose or life-threatening toxicity due to flurouracil or capecitabine.
References
1. Ashour, O.M., Naguib, F.N.M., and el Kouni, M.H. 5-(m-Benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2',3',5'-tri-O-acetyluridine, a prodrug of uridine, as modulators of plasma uridine concentration: Implications for chemotherapy. Biochem. Pharmacol. 51(12), 1601-1611 (1996).
2. Saydoff, J.A., Garcia, R.A.G., Browne, S.E., et al. Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse models of Huntington's disease. Neurobiol. Dis. 24(3), 455-465 (2006).
3. von Borstel, R.W., O'Neil, J.D., Saydoff, J.A., et al. Uridine triacetate for lethal 5-FU toxicity due to dihydropyrimidine dehydrogenase (DPD) deficiency. J. Clin. Oncol. 28(15_supp), e13505-e13505 (2010).